The overall objective of this research is to study the effects of viral interference on viral gene expression. In work already published, we have shown that clear plaque (C) mutants which arise in influenza virus populations can rapidly predominate in those hosts in which they can interfere with the replication of the parental virus (designated F for fuzzy plaque morphology). We wish to study the mechanism of this interference so that its role in the selection of mutants or recombinants can be evaluated. Specifically, we will (1) characterize the virion RNA by polyacrylamide gel electrophoresis and nucleotide fingerprinting so that we can determine which virion genome segments differ between the F and C variants, (2) compare the viral proteins from the two by tryptic peptide analysis and immunological methods (3) determine whether the capacity to interfere and to produce clear plaques is a consequence of a single mutational event, and (4) determine which gene functions are required for interference induction. This will be done by testing the interfering capacity of UV irradiated C virus, temperature sensitive C mutants, and virus strain which undergo abortive infection. Information from these experiments should let us determine whether interferences of this type can be important in the epidemiology of influenza, whether it significantly effects the outcome of genetic analysis of these viruses, and whether it can be employed to obtain virus strains of desired characteristics for vaccine use and for the investigation of virus properties such as virulence, transmissibility, and host range. The experiments should also provide information about the replication of the influenza viruses and about virus particle-induced interference.